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Association of plasma biomarkers of Alzheimer’s pathology and neurodegeneration with gait performance in older adults
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Association of plasma biomarkers of Alzheimer’s pathology and neurodegeneration with gait performance in older adults
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Journal Article
Association of plasma biomarkers of Alzheimer’s pathology and neurodegeneration with gait performance in older adults
2025
Overview
Background
Declining gait performance is seen in aging individuals, due to neural and systemic factors. Plasma biomarkers provide an accessible way to assess evolving brain changes; non-specific neurodegeneration (NfL, GFAP) or evolving Alzheimer’s disease (Aβ 42/40 ratio, P-Tau181).
Methods
In a population-based cohort of older adults, we evaluate the hypothesis that plasma biomarkers of neurodegeneration and Alzheimer’s Disease pathology are associated with worse gait performance. A sample of 2641 Mayo Clinic Study of Aging participants with measurements of plasma biomarkers and gait parameters was analyzed in this cross-sectional study. Linear regression models using plasma biomarkers as predictors of gait parameters and adjusted for age, sex, BMI, Charlson Comorbidity Index, and cognitive diagnosis were evaluated.
Results
In this study multiple statistically significant relationships are observed for GFAP, NfL, and P-Tau181 with gait parameters. Each standard deviation increase in GFAP, NfL, and P-Tau181 is associated with a reduction in velocity of 2.100 (95% CI: −3.004, −1.196;
p
= 5.4 × 10
−6
), 4.400 (−5.292, -3.507;
p
= 9.5 × 10
−22
), and 2.617 (−3.414, −1.819;
p
= 1.5 × 10
−10
) cm/sec, respectively. Overall, NfL has the strongest associations with poor gait performance. Models with age interactions show that the strength of associations between the plasma biomarkers and the gait parameters became stronger with increasing age. There are no specific gait parameters that associate with individual plasma biomarkers.
Conclusion
Plasma biomarkers of neurodegeneration and Alzheimer’s Disease pathology are not only markers of cognitive decline but also indicate motor decline in the aging population.
Ali, Syrjanen et al. examine the relationship between plasma biomarkers of Alzheimer’s disease pathology and neurodegeneration and their impact on gait performance in older adults. Elevated biomarkers correlate with diminished gait functionality, suggesting motor function decline is indicated alongside cognitive impairment in the aging population.
Plain language summary
Decline in gait and balance occurs as an individual gets older. These changes can increase risk for falls, death and disability. However, the brain changes that cause a declining gait and balance in aging are incompletely understood. Here, we evaluated gait performance in over 2000 individuals as well as blood biomarkers that indicate evolving Alzheimer’s disease or neurodegeneration. We found that gait changes in the aging individual are associated with neurodegeneration and accumulation of Alzheimer’s disease pathology independent of their memory performance. These findings offer evidence for the role of blood biomarkers in investigating gait decline. Future research will build upon these findings to expand our understanding of brain mechanisms that contribute to gait and balance abnormalities in aging individuals.
